Recent studies in our laboratory have shown that fasting in rats significantly reduces sympathetic activity with prompt reversal by refeeding. The implications of this finding are considerable in light of the potential role of the sympathetic nervous system in the pathogenesis of hypertension, diabetes, ischemic heart disease, and cardiac arrhythmias. The studies proposed here seek to extend these observations to man as well as to elucidate further the relationship between carbohydrate metabolism and the sympathoadrenal system. Studies are planned to evaluate the effect of nutrition on the activity of the sympathetic nerves and the adrenal medulla. Studies in rats, utilizing tracer norepinephrine (NE) to measure NE turnover will assess the effect of carbohydrate, protein, and fat intake on sympathetic activity in pregnancy will be studied in the same manner. Correlation between the effect of these diets and physiologic states on NE turnover and blood pressure will be determined. Parallel studies in metabolic cages will assess the urinary excretion of NE and epinephrine (E) under the conditions. The effect of changes in sympathetic activity in vivo on glycogen storage in liver and the hormonal responses of the endocrine pancreas will be assessed as well. Studies on human subjects will utilze measurement of plasma NE levels, dopamine-beta-hydroxylase activity, and urinary catecholamine excretion to assess the effect of fasting and alterations in diet on sympathoadrenal activity in man. Normal, obese, hypertensive, pregnant and diabetic subjects will be studied, as well as patients with diabetic ketoacidosis and hyperosmolar coma. The long term goal of this research is improved therapeutics based on a better understanding of the role of nutritional factors in determining the activity of the sympathoadrenal activity. The studies proposed here may have implications for the treatment of obesity, hypertension, diabetes and ischemic heart disease.